Particle analyzing system for coulter particle device and method

ABSTRACT

The output of a Coulter particle analysis device is converted into a computer acceptable code and stored in the computer in accordance with particle size information available for recall automatically or on command.

United States Patent Klein et al.

PARTICLE ANALYZING SYSTEM FOR COULTER PARTICLE DEVICE AND METHOD l nventors: Robert I. Klein, Hialeah; Walter R.

Hogg, Miami Lakes, both of Fla.

Assignee: Coulter Electronics, Inc., Hialeah,

Flap

Filed: Aug. 30, 1971 Appl. No.: 176,101

US. Cl. 235/92 PC, 235/92 R, 235/92 PB,

340/347 NT Int. Cl. G06m 11/04 Field of Search 235/92 PB, 92 PC;

340/347 NT, 347 SH, 347 AD Jan. 1, 1974 Primary Examiner-Maynard R. Wilbur Assistant Examiner-Robert F. Gnuse Attorney-l. Irving Silverman et al.

[57] ABSTRACT The output of a Coulter particle analysis device is converted into a computer acceptable code and stored in the computer in accordance with particle size information available for recall automatically or on command.

9 Claims, 2. Drawing Figures PARTICLE ANALYZING SYSTEM FOR COULTER PARTICLE DEVICE AND METHOD BACKGROUND OF THE INVENTION The Coulter particle analysis device disclosed in US. Pat. No. 2,656,508 has an output in the form of a string of particle-produced pulses, each pulse being substantially proportional in amplitude to the size of the respective particle scanned by the detecting and scanning means of the device. In this analog form, the particles could be counted and sized, but in order to utilize a computer, the data had to be reduced or predigested beforehand. Thereafter, if manually or automatically applied to a computer, the data could be stored and made available in a form suitable for statistical use.

SUMMARY OF THE INVENTION The invention herein enables the data from the Coulter particle analysis device to pass directly into a computer, thereby eliminating the need for an intermediate memory or for any reduction or analyzing of data or processing before being put. into the computer.

More specifically, the output of a Coulter particle analysis device is changed by conversion from analog to digital form into a computer-acceptable code and is fed to a computer where it is stored in its proper category and is available for extraction in computed form.

In one embodiment of the invention, peak detection is employed with sample-and hold and inhibit means; whereas, in another embodiment, a linearity improvement circuit is employed prior to transmitting the data to thecomputer. In both embodiments, the detection of the same relative instantaneous valve for each particle-produced pulse is employed prior to transmitting the data to the computer. I

BRIEF DESCRIPTION OF THE DRAWING FIG. 1 is a block diagram showing an embodiment of the invention and apparatus for use in practicing the method; and

FIG. 2 is a block diagram similar to that of FIG. 1, showing a modified form of the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The system of the invention is designated by the numeral 10. In FIG. 1 the Coulter particle device 12 produces a string of pulses at 14, each pulse having an amplitude which is proportional to the size of the particle which produced the same in the scanning and detecting portion of the Coulter device. The pulses pass through a gate 16 to the line 18 from which they are applied to a sample-and-hold circuit 20 and a peak detector 22. The output of the sample-and-hold circuit is at 24 and is applied to the analog-to-digital converter 26. The peak detector 22, whichcan be said to detect the same relative instantaneous value for each particle-produced pulse, serves as a system trigger to initiate the sampleand-hold function in the circuit 20 so that the A/D converter will be enabled by a pulse coming in on the line 24.

When the peak detector 22 is energized by a pulse, it produces an output at 28 when the pulse peak is reached. This output signal, besides triggering the sample-and-hold circuit, also energizes the A/D converter on the line 30 and pulses the inhibit device 32 through the line 34. The inhibit device 32 is enabled at this time and thereafter disables the gate 16 through the line 36 so that no incoming pulses will be accepted until the pulse being processed has completed its course through the system. a

In addition, the original signal is applied to the inhibit device 32 via the path 38, for use in preventing the gate 16 from being turned back on during a closelyfollowing pulse, as this would result in the analysis of a partial-pulse. The loss of any such pulse would be corrected by coincidence correction program. When the output from the A/D converter 26 has been produced and the computer 42 has accepted the data, there is a reset signal on the line 40, which removes the disabling signal from the line 36 and opens the gate 16, provided there is no signal on line 38. The inhibit device 32 logically may be two RS flip-flops, both of which are set by the signal on the line 34, and reset by the signals or lack thereof on lines 40 and 38. Their outputs would be ORed so that to process the next pulse, they both would have to be reset to remove the inhibit signal from the line 36. The inhibit device 32 could be a one-shot multivibrator, in which case thetime of disablement is fixed by the characteristics of the output of the oneshot and there is no need for the reset line 40.

The output of the A/D converter appears on a group of lines 44, such as for example eight such, and the output is connected directly to the computer 42 through an interface 46. The output of the interface 46 is shown at 48, consisting of the same number of lines. The interface inserts the digital output by proper address into the memory of the computer 42, this being done in a categorization of number of particles in accordance with their size. The categorization conveniently comprises a plurality of size ranges. Each time that the computer 42 receives an address from the interface that represents a particular range, the computer recalls the data from the memory location individual to that particular range, adds the new information and returns the resulting data to that memory location. In this manner, the computer has a total count for each size range automatically and directly inserted into its memory. It may, at the same time, have a location in its memory which gives total count irrespective of range, or combinations of ranges. For particle concentration measurements, stop-start control would be provided by the path 47 to terminate a count after a predetermined sample volume has been scanned. The line 49 is a data ready line from the A/D converter to the interface 46 to advise that the data is ready for the computer. Reset occurs when the computer has taken the data.

When the computer has received a predetermined number of inputs in any range, or channel as it is known, or' a total count, the system may be programmed to disable its input. This is accomplished by suitable programming. Such programming may also call for the computer to begin an output cycle through the line 50, for example, through the interface 52 to some peripheral equipment, such as the terminal 54, which may be a line printer, and the data output may be in the form of a listing of the channels giving the number of particles in eachchannel. The terminal 54 could be a recorder which produces a graph of the number of particles versus range. At the same time, the total count also may be printed out. Many different forms of output could be programmed.

Also or alternately, there may be an interactive terminal 56, such as a CRT terminal or teletype, which can display or read out the data or portions thereof and also provide system control for extracting information on command. In command situations, programming will occur by operating a keyboard. The interactive terminal S6 is shown with its interface 58 and its command line 60.

FIG. 2 is almost the same as FIG. 1, except that in stead of the sample-and-hold circuit 20, the linearity improvement circuit 62 is inserted between the gate 16 and the A/D converter 26. This may be a circuit similar to those described in copending U.S. Pat. application Ser. No. 48,888 filed June 15, 1970 now U.S. Pat. No. 3,668,531. Such a circuit improves the linearity of the Coulter particle device 12 by measuring particle pulses at the instantaneous valve which is at their approximate center instead of at their peak amplitudes. This is accomplished by integrating each of the pulses, comparing the original pulse with the integrated pulse, with the amplitudes of the two pulses adjusted so that they are the same at that instant corresponding to the time the particle producing the pulse is accurately centered in the scanning aperture of the scanning and detecting portion of the Coulter device. Since this circuit 62 incorporates an integrator, it is convenient to prevent the further rise of the integrator output at that instant when its amplitude is equal to that of the incoming particle pulse, thus holding a voltagevalve in its memory corresponding to the volume of the particle. This held voltage value is applied via the path 24 to the A/D converter 26.

When the A/D converter is finished making a conversion, the integrator in the linearity improvement circuit 62 may be reset or shortedout via the line 30, preparatory to the next pulse analysis. The A/D converter, by

the path 34, causes the inhibit logic device 32 to prevent particle pulses from being applied to the linearity improved circuit 62 by means of an inhibit pulse on the line 36. The threshold circuit 64 is included to permit the interface 46 to count the highest number of pulses regardless of the fact that the A/D converter will occasionally be so slow as to prevent the analysis of the second of two closely spaced pulses.

Since it is usually necessary that the computer has stored in it a particle frequency-vs-volume distribution for use in making statistical analyses, it is not necessary that all of the particles be analyzed and their volumes stored in the computer. It is only necessary that a good random sample of these particles be analyzed. Thus the addition of the circuit 62 merely extends the length of time necessary to get a correct representation of particle volumes in a statistically equivalent sample. If the count is'needed of all particles, regardless of particle volume, the particle pulses are fed by the path 66 to the threshold circuit 64, which is assumed to have built into it a voltage reference level, such that all particles regardless of size may be counted. This circuit emits for each particle a pulse at path 68 for transmission to the interface 46. The number of these particles would be stored in one address of the computer 42, and this address would thus store the total of particles in a given volume of sample. Although not shown in FIG. 1, the threshold circuit 64 and its input and output lines 66 and 68 can be coupled in the same manner as shown in FIG. 2 and for the same purpose as just described. It is assumed that the stop-start means of the Coulter particle device 12 is also fed to the interface 46 via the path 47 in order that the particle concentration may be stored also in the computer. Coincidence correction could be programmed into the computer.

Suitable noise exclusion'circuits will be included in the system 10, as for example, from the line 14 to the gate 16 as a separate input to prevent lock-up on noise, etc.

What it is desired to secure by Letters Patent of the United States is:

We claim: 1. A method for directly entering analog data from a Coulter particle analyzing device into the memory portion of a digital computer for further data analysis, the Coulter analyzing device scanning particles one at a time and producing a particle representative pulse for each scanned particle, said method comprising: detecting the same relative instantaneous analog valve for each particle-produced pulse, holding each instantaneous analog valve detected and converting that valve, while being held, into a computer-acceptable digitized valve, presenting each digitized valve to the computer memory portion'through suitable intervening interfacing structure which addresses different locations in the memory portion according to the magnitude of each digitized valve, storing in the computer the digitized data from a string of such pulses and in a form to enable analyzing the data in said computer, extracting that data from the computer in useful form, and monitoring each pulse prior to said detecting and also during said presenting for inhibiting said detecting of any following pulses during said converting and presenting and for a duration thereafter when a partial-pulse might be detected.

2. Apparatus for entering data from a Coulter particle analyzing device into a computer directly. for further data analysis which comprises: a Coulter particle analyzing device having an output comprising a string of pulses each having an amplitude substantially proportional to a respective particle producing same, instantaneous valve pulse detecting means coupled to receive said pulses, an A/D'converter coupled to the output of said instantaneous valve pulse detecting means, a computer for receiving the output of said AID converter, an address-assigning interface coupled between said computer and said A/D converter, gate means coupled between said Coulter particle analyzing device and said instantaneous valve pulse detecting means, an inhibit device having an inhibit output coupled to control said gate for effecting the closing of said gate for the length of an inhibit output signal, said inhibit device being coupled to be separately responsive to each pulse directly from said Coulter analyzing device and also to one of said instantaneous valve pulse detecting means and said A/D converter for generating an inhibit output signal until such time that said apparatus is ready to process a subsequent complete pulse from the Coulter particle analyzing device.

3. Apparatus according to claim 2 in which said interface has an output connected to said inhibit device for effecting the opening of said gate in the absence of said inhibit output signal.

4. Apparatus for entering data from a Coulter particle analyzing device into a computer directly for further data analysis which comprises: a Coulter particle analyzing device having an output comprising a string of pulses each having an amplitude substantially proportional to a respective particle producing same, instantaneous valve pulse detecting means coupled to receive said pulses, an A/D converter coupled to the output of said instantaneous valve pulse detecting means, gate means coupled between said Coulter particle analyzing device and said instantaneous valve pulse detecting means, an inhibit device which includes a one-shot multivibrator, said inhibit device coupled to be responsive to one of said instantaneous valve pulse detecting means and said A/D converter and having an output coupled to control said gate for effecting the closing of said gate for the length of the output signal of said multivibrator, a computer for receiving the output of said A/D converter, and an address-assigning interface coupled between said computer and said A/D converter.

5. Apparatus according to claim 4 in which said instantaneous valve pulse detecting means comprises peak detecting means and a sample-and-hold means both connected to receive said pulses, said AID converter being coupled to the output of said sample-andhold means, and both said A/D converter and sampleand-hold means being rendered operative by the output of said peak detector.

6. Apparatus for entering data from a Coulter particle analyzing device into a computer directly for further data analysis which comprises: a Coulter particle analyzing device having an output comprising a string of pulses each having an amplitude substantially proportional to a respective particle producing same, instantaneous value pulse detecting means coupled to receive said pulses, an A/D converter coupled to the output of said instantaneous valve pulse detecting means,

gate means coupled between said Coulter particle analyzing device and said instantaneous valve pulse detecting means, an inhibit device which includes a R.S. flipflop coupled to be set by one of said instantaneous valve pulse'detecting means and said A/D converter and having an output coupled to control said gate for effecting the closing of said gate for the length of time that said flip-flop is set, a computer for receiving the output of said A/D converter, and an address-assigning interface coupled between said computer and said A/D converter.

7. Apparatus according to claim 6 in which said R.S. flip-flop is coupled to said interface to be reset thereby for the opening of said gate.

8. Apparatus according to claim 7 in which said inhibit device has an inhibit input coupled to the output of said Coulter particle analyzing device, and said inhibit device is constructed so that said gate cannot be opened during the time that a pulse is at the output of said Coulter particle analyzing device.

9. Apparatus for entering analog data from a Coulter particle analyzing device into a plurality of different 10- cations in the memory of a digital computer for data analysis which comprises: a Coulter particle analyzing device having an output comprising a string of analog pulses each having an amplitude substantially proportional to the volume of a respective particle producing same, instantaneous valve pulse detecting means connected to receive said analog pulse, an A/D converter coupled to the output of said instantaneous valve pulse detecting means for providing at its output a digitized volume valve for each particle, an interface coupled to the output of said A/D converter, said, interface constructed to assign to each'digitized valve one of a plurality of computer memory location addresses based upon a corresponding plurality of different particle volume ranges, a digital computer for receiving the addressed output from the interface, said computer including an addressable plural location memory and means for cumulatively entering into each memory location the number of detected pulses lying within its corresponding particle volume range, and pulse gating and inhibit means coupled between said Coulter particle analyzing device and said instantaneous valve pulse detecting means, said pulse gating inhibit means being constructed and arranged to be responsive at least to each analog pulse which appears at the output of said Coulter particle analyzing device at the time that said interface is addressing said computer with respect to a prior pulse, for inhibiting the gating of any partial pulse to said instantaneous valve pulse detecting means at the end of said addressing time. the output of said Coulter particle analyzing device at the time that said interface is addressing said computer with respect to a prior pulse, for inhibiting the gating of any partial pulse to said instantaneous value pulse detecting means at the end of said addressing time.

I "UNITED STATES PATENT OFFICE I CERTIFICATE OF CORRECTION Patent No. 3,783,247 I Dated January 1, 1974 Inven or -RQBERT I. KLEIN, et al.

It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 3, line 15, change "valve" to valueline 37, change "improved" to -improvement--. In each of the following locations and for, all occurrences, change "valve" to -'-'value---: Column 4, lines'l 6, 18 20, 24', 39 41, 46,52, and 67. Column 5 lines 2, 4, 7, 15, 30, 32-, and 35. Column 6, lines 14, 16,

'18, 20, 30, and 37. Column 6, lines 38' through 44, delete "the output. time period". I

. Signed and sealed this 11th day of June 1971;;

. (SEAL) Attest: p p I H p EIMARD mmLm'cnamjJm I w A C MARSHALL 1mm Attesting Officer Commissioner of Patents. 7

FORM 0-69) I 4 v usc'oMM-oc 60376-P69 i U.S, GOVERNMENT I'RINTING OFFICE I!" 0-36l-33L 

1. A method for directly entering analog data from a Coulter particle analyzing device into the memory portion of a digital computer for further data analysis, the Coulter analyzing device scanning particles one at a time and producing a particle representative pulse for each scanned particle, said method comprising: detecting the same relative instantaneous analog valve for each particle-produced pulse, holding each instantaneous analog valve detected and converting that valve, while being held, into a computer-acceptable digitized valve, presenting each digitized valve to the computer memory portion through suitable intervening interfacing structure which addresses different locations in the memory portion according to the magnitude of each digitized valve, storing in the computer the digitized data from a string of such pulses and in a form to enable analyzing the data in said computer, extracting that data from the computer in useful form, and monitoring each pulse prior to said detecting and also during said presenting for inhibiting said detecting of any following pulses during said converting and presenting and for a duration thereafter when a partial-pulse might be detected.
 2. Apparatus for entering data from a Coulter particle analyzing device into a computer directly for further data analysis which comprises: a Coulter particle analyzing device having an output comprising a string of pulses each having an amplitude substantially proportional to a respective particle producing same, instantaneous valve pulse detecting means coupled to receive said pulses, an A/D converter coupled to the output of said instantaneous valve pulse detecting means, a computer for receiving the output of said A/D converter, an address-assigning interface coupled between said computer and said A/D converter, gate means coupled between said Coulter particle analyzing device and said instantaneous valve pulse detecting means, an inhibit device having an inhibit output coupled to control said gate for effecting the closing of said gate for the length of an inhibit output signal, said inhibit device being coupled to be separately responsive to each pulse directly from said Coulter analyzing device and also to one of said instantaneous valve pulse detecting means and said A/D converter for generating an inhibit output signal until such time that said apparatus is ready to process a subsequent complete pulse from the Coulter particle analyzing device.
 3. Apparatus according to claim 2 in which said interface has an output connected to said inhibit device for effecting the opening of said gate in the absence of said inhibit output signal.
 4. Apparatus for entering data from a Coulter particle analyzing device into a computer directly for further data analysis which comprises: a Coulter particle analyzing device having an output comprising a string of pulses each having an amplitude substantially proportional to a respective particle producing same, instantaneous valve pulse detecting means coupled to receive said pulses, an A/D converter coupled to the output of said instantaneous valve pulse detecting means, gate means coupled between said Coulter particle analyzing device and said instantaneous valve pulse detecting means, an inhibit device which includes a one-shot multivibrator, said inhibit device coupled to be responsive to one of said instantaneous valve pulse detecting means and said A/D converter and having an output coupled to control said gate for effecting the closing of said gate for the length of the output signal of said multivibrator, a computer for receiving the output of said A/D converter, and an address-assigning interface coupled between said computer and said A/D converter.
 5. Apparatus according to claim 4 in which said instantaneous valve pulse detecting means comprises peak detecting means and a sample-and-hold means both connected to receive said pulses, said A/D converter being coupled to the output of said sample-and-hold means, and both said A/D converter and sample-and-hold means being rendered operative by the output of said peak detector.
 6. Apparatus for entering data from a Coulter particle analyzing device into a computer directly for further data analysis which comprises: a Coulter particle analyzing device having an output comprising a string of pulses each having an amplitude substantially proportional to a respective particle producing same, instantaneous value pulse detecting meanS coupled to receive said pulses, an A/D converter coupled to the output of said instantaneous valve pulse detecting means, gate means coupled between said Coulter particle analyzing device and said instantaneous valve pulse detecting means, an inhibit device which includes a R.S. flip-flop coupled to be set by one of said instantaneous valve pulse detecting means and said A/D converter and having an output coupled to control said gate for effecting the closing of said gate for the length of time that said flip-flop is set, a computer for receiving the output of said A/D converter, and an address-assigning interface coupled between said computer and said A/D converter.
 7. Apparatus according to claim 6 in which said R.S. flip-flop is coupled to said interface to be reset thereby for the opening of said gate.
 8. Apparatus according to claim 7 in which said inhibit device has an inhibit input coupled to the output of said Coulter particle analyzing device, and said inhibit device is constructed so that said gate cannot be opened during the time that a pulse is at the output of said Coulter particle analyzing device.
 9. Apparatus for entering analog data from a Coulter particle analyzing device into a plurality of different locations in the memory of a digital computer for data analysis which comprises: a Coulter particle analyzing device having an output comprising a string of analog pulses each having an amplitude substantially proportional to the volume of a respective particle producing same, instantaneous valve pulse detecting means connected to receive said analog pulse, an A/D converter coupled to the output of said instantaneous valve pulse detecting means for providing at its output a digitized volume valve for each particle, an interface coupled to the output of said A/D converter, said, interface constructed to assign to each digitized valve one of a plurality of computer memory location addresses based upon a corresponding plurality of different particle volume ranges, a digital computer for receiving the addressed output from the interface, said computer including an addressable plural location memory and means for cumulatively entering into each memory location the number of detected pulses lying within its corresponding particle volume range, and pulse gating and inhibit means coupled between said Coulter particle analyzing device and said instantaneous valve pulse detecting means, said pulse gating inhibit means being constructed and arranged to be responsive at least to each analog pulse which appears at the output of said Coulter particle analyzing device at the time that said interface is addressing said computer with respect to a prior pulse, for inhibiting the gating of any partial pulse to said instantaneous valve pulse detecting means at the end of said addressing time, the output of said Coulter particle analyzing device at the time that said interface is addressing said computer with respect to a prior pulse, for inhibiting the gating of any partial pulse to said instantaneous value pulse detecting means at the end of said addressing time. 